rs1421023094
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP3BP6_Moderate
The NM_000069.3(CACNA1S):c.4114-5T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
CACNA1S
NM_000069.3 splice_region, splice_polypyrimidine_tract, intron
NM_000069.3 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9994
2
Clinical Significance
Conservation
PhyloP100: 1.21
Genes affected
CACNA1S (HGNC:1397): (calcium voltage-gated channel subunit alpha1 S) This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 1-201050521-A-T is Benign according to our data. Variant chr1-201050521-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 541044.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1S | NM_000069.3 | c.4114-5T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000362061.4 | |||
CACNA1S | XM_005245478.4 | c.4057-5T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1S | ENST00000362061.4 | c.4114-5T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000069.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000205 AC: 3AN: 1461770Hom.: 1 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727178
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
3
AN:
1461770
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
727178
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at